Osteoarthritis is the most common joint disease among the rheumatic disorders affecting the Western world. It is a chronic degenerative joint disease which may be diffuse or localised, affecting the cartilage of the diarthrodial joints, where the normal metabolic process of the chondrocytes is impaired, leading to softening, fibrillation, ulceration and subsequent sclerosis of the subchondral bone, and in the final stages to new bone formation and subchondral cysts.
Osteoarthritis, which mainly affects women, most frequently involves the patellofemoral joint, the femorotibial joint, the hip and the shoulder. Osteoarthritis of the knee, or gonarthritis, is particularly frequent and disabling. The clinical picture is initially dominated by characteristically mechanical pain at the anterior or anteromedial site, which is attenuated by rest. After lengthy inactivity, for example in the mornings or after sitting for a long time, painful post-inactivity spasms may be experienced. However, they are shortlived, and attenuated by walking. Pain may be triggered by using stairs, especially walking downstairs, squatting, especially in the case of patellofemoral osteoarthritis, or lengthy use of vehicle pedals. Initially there may also be pain in the periarticular areas, and modest effusion. The pain may later affect the whole joint, become nocturnal, and be accompanied by frequent joint effusions. Functional impairment only appears at a late stage, despite the presence of a considerable valgus or varus malalignment.
Until a few years ago the main therapeutic objective of the treatment of knee osteoarthritis was controlling the symptoms (pain and functional limitation), traditionally achieved with NSAIDs (non-steroidal anti-inflammatory drugs) and other painkillers.
The ideal treatment of knee osteoarthritis requires a combination of pharmacological and other treatments, which must be tailored to the patient's requirements on the basis of local risk factors (obesity, mechanical factors, physical activity), general risk factors (age, comorbidity, multiple drug therapy), pain intensity levels and degree of disability, signs of inflammation (effusion), location and degree of structural damage.
Non-pharmacological treatment of knee osteoarthritis should include rehabilitation programmes, physical exercise, the use of aids (walking sticks, insoles or knee braces) and weight loss, where necessary.
The first-line medicament for the treatment of pain in knee osteoarthritis is paracetamol, which is used at doses lower than or equal to 3 gm/day in addition to other osteoarthritis drugs.
Topical applications of NSAIDs or capsaicin can be a useful treatment if used for short periods, especially for patients who refuse or are unable to take oral medicaments.
NSAIDs are considered for patients who fail to respond to paracetamol and patients at gastrointestinal risk; in that case, conventional COXIBs or NSAIDs associated with proton pump inhibitors are used.
Opioid analgesics represent useful alternatives in patients for whom NSAIDs or COXIBs are contraindicated because they are ineffective or poorly tolerated.
Other drugs used are those which, when administered by the oral or intra-articular route, reduce the clinical symptoms at varying rates, by different methods from analgesics or NSAIDs. This group consists of two different categories: slow-acting symptomatic medicaments for osteoarthritis, and medicaments able to modify the progress of osteoarthritis. Glucosamine sulphate, chondroitin sulphate, soya and avocado extracts, diacerein, hyaluronic acid and S-adenosylmethionine belong to the first group. These medicaments have a direct action on the chondrocytes and synoviocytes and consequently have beneficial effects on the cartilage structure. Their efficacy against the symptoms starts slowly (1-2 weeks) but lasts for a long time: up to two months after discontinuance of the treatment.
Intra-articular injection of cortisones with a long-lasting action is indicated for acute joint pain, especially if it is associated with intra-articular effusions.
Research currently focuses on molecules with specific effects on the pathogenetic mechanisms of osteoarthritis, modifying both the symptoms and the joint structure to counteract the progress of the disease.
International patent application PCT/EP2006/009966 describes wound-healing pharmaceutical compositions comprising a combination of glycine, lysine, leucine and proline and sodium hyaluronan, which is particularly effective in facilitating the cell renewal process that forms the basis of rapid wound-healing, promoting connective tissue reconstruction and consequent regeneration of the epithelial cells.